Compared to traditional macroelectrodes, nanoscale electrodes have tremendous potential when employed in electrochemical-based sensing; due to enhanced sensitivity arising from increased mass transport to the electrode (convergent, 3D-diffusion). Discrete nanowire devices have excellent limits of detection (pM-nM), high signal to noise (S/N) ratios (10,000), with 1000 fold increase in sensitivity compared to commercial ultra-microelectrodes.
A critical challenge when employing on chip nanoscale electrodes is that not only does this internal electrostatic field arise at the electrode (nanowire) it is observed to be present at the insulator surface above the on-chip interconnect tracks, consequently increasing the background signal, and reducing the sensitivity of such devices as functioning sensors.
Nanoelectrodes offer a number of enhancements compared to macroelectrodes due to their many advantageous properties: low background charging, high current density due to enhanced mass transport, low depletion of target molecules, low supporting electrolyte concentrations, and shorter RC time constant. These advantages contribute to the improved signal to noise ratios (S/N) that can make sensor electrodes based on nanowires highly desirable as biosensor devices. However, practical challenges remain in order to deliver electrochemical-based nanosensors with real world applications. Currently, discrete nanowire sensors typically have measureable currents in the nA regime (1-10 nA) and noise values in pA regime (<5 pA). For higher sensitivity, the magnitude of the measureable signal needs to be increased, while maintaining the advantages of low noises levels.
The first approach is to reduce the noise contribution, which would not only improve the S/N but also improve the limit of detection. Noise in electrochemical based sensors is typically attributed to capacitive current, arising from the build-up of charge in the electrolyte when a voltage bias is applied to an electrode. At nanoelectrodes fabricated on silicon substrates stray capacitive noise can arise from the build-up of charge over the dielectric layer above the on chip interconnection metallisation. The magnitude of the resulting noise is also dependent of the measurement duration and at short measurement times; desirable for rapid analysis, the level of noise is dramatically increased. It is highly desirable to eliminate this capacitive noise in order to achieve (i) higher S/N ratios (thereby increased sensitivity) and (ii) rapid (sub 1 second) electrochemical analysis times.
A second approach is to increase the magnitude of the measureable signal is to employ connected arrays of long (>100 microns) discrete nanowires which would facilitate acquisition of higher measurable currents. However, the separation (gaps) between individual nanowires within an array is critical to the sensor performance. For electrochemical fixed potential or potential sweep techniques such as linear sweep or cyclic voltammetry, maximum efficiency may be obtained when the nanowires are sufficiently separated, allowing independent diffusion profiles between neighbouring nanowires to exist, in turn giving rise to diffusional independence. Alternatively, electrochemical sensing based on applied potential pulse techniques such as square wave or differential pulse voltammetry, maximum efficiency may be obtained when the nanowires are relatively close to each other so that diffusion profiles of adjacent nanowire electrodes in an array overlap. Diffusion modelling is therefore critical to inform design in order to enable fabrication of nanowires enabling maximum efficiency depending on the sensing technique employed.
The requirement of low sample volumes and the need to minimise cell resistances necessitates the requirement for integrated on-chip counter and reference electrodes. However, the sensitivity of nanowire sensors is such, that dissociated silver and chloride ions diffusing from a typical Ag/AgCl reference electrode are detectable resulting in electrochemical peaks that could interfere with the detection of key target analytes. This precludes their use as a suitable reference material, consequently new quasi reference materials will be required based on pure metals that would provide a stable reference voltage and are easy to maintain.
It is therefore an object of the invention to provide a nanowire based sensor system and method to overcome at least one of the above mentioned problems.